Chronic administration of opiates produces a dependent state which is generally characterized by abstinence behavior when opiate intake is abruptly terminated or when an opiate antagonist is administered. Recently, a number of investigators have shown that fragments of Beta-lipotropin (LPH) have opiate angonist activities when bioassayed in mouse vas deferens, guinea pig ileum or stereo-specific binding to purified brain extracts. Of the active lipoprotein fragments, we have shown that Beta-endorphin (LPH 61-91) in particular, is a potent analgesic agent. In comparing the pharmacological properties of opiate-like peptides to opiate alkaloids, it is of importance to know if these peptides can cause physical dependence. The development of a novel technique of drug delivery, the osmotic minipump system, has enabled me to show that chronic exposure to methionine-enkephalin and Beta-endorphin can result in physical dependence. In the coming year, I intend to: 1) Compare the behavioral and cardiovascular effects of Beta-endorphin, enkephalin analogs, and morphine and define those pharmacological actions which are specifically related to the development of physical dependence. 2) Establish the basic conditions for using the osmotic minipump technique in the bioassay of the potency of opioid peptides for producing physical dependence. 3) Determine if the agonist potency of an opiate or opioid peptide is inevitably correlated to potency for producing physical dependence. 4) Determine the brain sites where physical dependence develops after chronic infusion of opiates into localized brain regions. BIBLIOGRAPHIC REFERENCES: H. Loh, L.F. Tseng, E. Wei and C.H. Li. Beta-Endorphin is a potent analgesic agent. Proceedings of the National Academy of Sciences 73: 2895-2898. 1976. P.Y. Law, E.T. Wei, L.F. Tseng, H.H. Loh & E.L. Way. Opioid properties of Beta-lipoprotein fragment 60-65, H-Arg-Tyr-Gly-Gly-Phe-Met-OH. Life Sciences 20: 251-260, 1977.